{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:10:43Z","timestamp":1792084243932,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005725","name":"CHDI Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["223082\/Z\/21\/Z"],"award-info":[{"award-number":["223082\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Huntington's disease (HD) is characterized by early, selective, progressive vulnerability of striatal medium spiny neurons (MSNs). Proenkephalin (PENK), a precursor of opioid peptides abundantly expressed in MSNs, is a promising biomarker of striatal integrity, but region\u2010specific associations and its potential for early\u2010stage discrimination have not been characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We investigated cross\u2010sectional and longitudinal associations between baseline cerebrospinal fluid (CSF) PENK concentration and regional brain atrophy, compared identified patterns with CSF neurofilament light (NfL), and evaluated PENK and NfL for discriminating between HD Integrated Staging System (HD\u2010ISS) stage 0 versus 1 in a far\u2010from\u2010onset HD gene\u2010expanded (HDGE) cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole\u2010brain voxel\u2010based morphometry was performed in 149 participants (72 HDGE, 77 controls) cross\u2010sectionally and 88 participants (54 HDGE, 34 controls) longitudinally over a mean interval of 4.8\u2009years. Voxel\u2010wise linear regression tested associations between baseline biofluid biomarkers and gray\/white matter volume, adjusting for age, sex and CAG\u2010Age Product score, with false discovery rate correction. Logistic regression and receiver operating characteristic analyses assessed stage discrimination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Lower baseline CSF PENK predicted longitudinal gray and white matter loss, predominantly in the striatum bilaterally. Higher baseline CSF NfL predicted widespread longitudinal white matter loss. For stage discrimination, PENK (area under curve [AUC], 0.706;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0002) outperformed NfL (AUC, 0.661;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.1596) with minimal gain from combining both (AUC, 0.714; joint\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0007).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Lower baseline CSF PENK concentration predicted longitudinal striatal atrophy and CSF PENK outperformed CSF NfL in distinguishing HD\u2010ISS stages 0 and 1, supporting its role as a striatum\u2010specific biomarker with potential to enrich early\u2010stage HD trial cohorts. \u00a9 2025 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70062","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T08:54:41Z","timestamp":1758876881000},"page":"95-106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cerebrospinal Fluid Proenkephalin Predicts Striatal Atrophy Decades before Clinical Motor Diagnosis in Huntington's Disease"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0679-0117","authenticated-orcid":false,"given":"Mena","family":"Farag","sequence":"first","affiliation":[{"name":"Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology University College London  London United 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Sweden"},{"name":"Dementia Research Institute University College London  London United Kingdom"},{"name":"Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology  London United Kingdom"},{"name":"Hong Kong Center for Neurodegenerative Diseases  Clear Water Bay Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7803-4679","authenticated-orcid":false,"given":"Douglas R.","family":"Langbehn","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Biostatistics, Carver College of Medicine and College of Public Health University of Iowa  Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren G.","family":"Monckton","sequence":"additional","affiliation":[{"name":"School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences University of Glasgow  Glasgow United 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